This invention relates to a method of inhibiting bacterial adhesion to biomaterials. More particularly, the invention relates to a method of reducing device-associated infections by inhibiting bacterial adhesion to biomaterials with apo-transferrin.
With over 200 million intravascular devices sold annually in the United States, it is apparent that biomedical devices have become an integral part of clinical medicine, and their use is increasing continuously. Infection and thrombosis are often major complications involved with all types of synthetic biomaterials that come in contact with blood, ranging from catheters to artificial hearts. It has been estimated that greater than 45% of hospital infections are related to implants and medical devices. As more devices are implanted and new devices are introduced into clinical use, increasing numbers of patients will be placed at risk for implant-related infection. These complications may be directly attributed to the presence of biomaterial, which is foreign to the human body and provides a suitable substrate for bacterial adhesion at a site sequestered from the body's immunological defenses.
Persistent bacterial infections associated with implant devices remain a serious and costly complication with both temporary and permanent implants. Clinical experience to date suggests that the adherence of bacteria to the biomaterial, resulting in subsequent colonization and biofilm formation, may be the critical event in the pathogenesis of implant-induced infection. Such infections typically are difficult to resolve with antimicrobial therapy, and have been identified as a major cause for patient morbidity, device failure, and explantation.
After blood contacts biomaterial, proteins adsorbed at the interface change the surface characteristics and may provide a suitable substrate for bacteria to adhere and proliferate. Upon bacterial colonization on the surface and formation of biofilm, such a sequestered site may permit pathogenic microorganisms to evade phagocytic cells as well as reduce effective penetration of antibiotics. In many instances, replacement of the infected device is the only successful treatment.
Since the pathogenesis of biomaterial-centered infection is critically dependent on the initial bacterial adhesion to and early growth on a surface, several strategies to disrupt the adhesion process have been suggested. These include incorporating antibiotics or immobilizing antimicrobial peptides into biomaterials and coating biomaterials with surfactants such as salicylic acid, silver, substituted dextran, or polyethylene oxide. The role of serum proteins in mediating bacterial adhesion has been well studied over the past decade. The present inventors, along with other investigators, have shown the antibacterial properties of serum. Recent publications have revealed a strong inhibition of adherence of certain bacteria to biomaterials by whole serum.
In view of the foregoing, it will be appreciated that providing a method for inhibiting bacterial adhesion to biomaterials and reducing infections associated therewith would be a significant advancement in the art.